CD4CD25Foxp3 regulatory T cells regulate immune balance in unexplained recurrent spontaneous abortion via the Toll-like receptor 4/nuclear factor-κB pathway.

OBJECTIVE

The present study aimed to evaluate the effects of cluster of differentiation (CD)4CD25 forkhead box p3 (Foxp3) regulatory T cells (Tregs) on unexplained recurrent spontaneous abortion (URSA) and the associated mechanisms.

METHODS

The proportion of CD4CD25Foxp3 Tregs and inflammatory cytokine concentrations in the peripheral blood of women with URSA were measured by flow cytometry and enzyme-linked immunosorbent assay, respectively. CBA/JxDBA/2J mating was used to establish an abortion-prone mouse model and the model mice were treated with the Toll-like receptor 4 (TLR4) antagonist E5564 and the TLR4 agonist lipopolysaccharide.

RESULTS

The proportion of CD4CD25Foxp3 Tregs was decreased and the inflammatory response was increased in women with URSA. In the abortion-prone mouse model, E5564 significantly increased the proportion of CD4CD25Foxp3 Tregs, decreased the inflammatory response, and increased Foxp3 mRNA and protein expression. Lipopolysaccharide had adverse effects on the abortion-prone model.

CONCLUSIONS

These data suggest that CD4CD25Foxp3 Tregs regulate immune homeostasis in URSA via the TLR4/nuclear factor-κB pathway, and that the TLR4 antagonist E5564 may be a novel and potential drug for treating URSA.